A Study of SYH2051 Monotherapy in Advanced Solid Tumors or in Combination With Radiotherapy in Locally Advanced Head and Neck Cancer

Inclusion Criteria:

1. Age ≥18 years old, male or female;
2. Phase Ia: Patients with histologically or cytologically confirmed advanced solid tumors, for whom there is no standard therapy available, or ineffective or intolerant to standard therapy. Phase Ib/Ic: Patients with histologically or cytologically confirmed locally advanced head and neck cancer suitable for radiotherapy alone;
3. Eastern Collaborative Oncology Group (ECOG) Performance Status of 0\~1;
4. Patients in medical conditions to be able to receive radiotherapy (for phase Ib/Ic);
5. Life expectancy of \>3 months;
6. At least one measurable lesion (excluding patients in phase Ic combined with adjuvant radiotherapy);
7. Patients with adequate hematologic, hepatic, renal and coagulation function;
8. Patients are not pregnant or lactating and required contraception;
9. Patients who are willing to provide written informed consent form (ICF) before the beginning of the study.

Exclusion Criteria:

1. Any antineoplastic therapy such as chemotherapy, biologic therapy, endocrine therapy, or immunotherapy within 4 weeks before the first dose of the study drug (or within 5 half-lives of other unmarketed study drugs, whichever is longer), except for the following:

   1. 6 weeks for Nitrosoureas or mitomycin C;
   2. 2 weeks or five half-lives (whichever is longer) for oral fluorouracil and small molecule targeted drugs;
   3. 2 weeks for Chinese herbal medicine with antineoplastic indications;
2. Patients with previous (within 2 years before screening) or concurrent other malignancies (only for phase Ib/Ic);
3. Patients had undergone major organ surgery (excluding needle biopsies) within 4 weeks before the first dose, with obvious trauma, or require elective surgery during the study;
4. Severe, non-healing fractures within 4 weeks before the first dose of the study drug;
5. The adverse reactions of previous antineoplastic therapy have not recovered to ≤grade 1 as determined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria;
6. Patients who had received treatment with any drug that is a medium or strong inhibitor or inducer of cytochrome P450 (CYP) 3A4/5 enzyme activity within 2 weeks before screening or need to continue receiving such drugs;
7. Active brain metastases and/or carcinomatous meningitis;
8. Concurrent serious and/or uncontrolled medical conditions at screening (e.g., severe chronic obstructive pulmonary disease);
9. Patients with abnormal thyroid function were not allowed, except those with euthyroid function after drug control;
10. History of severe cardiovascular disease;
11. History of myopathy or raised creatine kinase (CK) \>5 times the upper limit of normal (ULN);
12. Known hypersensitivity or intolerance to any component of the study drug or its excipients;
13. History of autoimmune disease, immunodeficiency disease, including HIV testing positive or other acquired, congenital immunodeficiency diseases, or organ transplantation;
14. Active hepatitis B virus, hepatitis C virus or active syphilis infection;
15. Active dysphagia, malabsorption or other chronic gastrointestinal diseases or conditions that may hamper compliance and/or absorption of the study drug;
16. Other ineligibilities according to the investigator.